Sharon See, PharmD

ABSTRACT

BACKGROUND: Outpatient management of symptoms from acute alcohol withdrawal usually includes a tapering regimen of a benzodiazepine such as lorazepam (Ativan). Benzodiazepine use is usually limited, however, by the potential for medication abuse and side effects such as central nervous system impairment. Because studies have demonstrated that carbamazepine can be effective for the treatment of alcohol withdrawal symptoms, this study compared the effectiveness of carbamazepine with that of lorazepam.
POPULATION STUDIED: The 136 patients were self-referred and fulfilled Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for alcohol dependence and alcohol withdrawal. Patients lived within 50 miles of the study site, and had an admission blood alcohol level < 0.1 g/dL, a Mini Mental State Examination score of 26, and an admission score on the Clinical Institute Withdrawal Assessment-Alcohol, revised (CIWA-Ar) 10 out of a possible score of 20. Patients were excluded if they had substance abuse syndromes other than alcohol dependence, nicotine dependence, or cannabis abuse; major Axis I psychiatric disorder; used benzodiazepines, beta-blockers, calcium channel blockers, or antipsychotic agents within the past 30 days; a history of head injury; neurologic illness; or grossly abnormal laboratory values.
STUDY DESIGN AND VALIDITY: This was a randomized double-blind trial comparing 2 different treatments for alcohol withdrawal. Allocation to treatment group was concealed from enrolling physicians. The patients received a 5-day taper of either lorazepam 6–8 mg tapered to 2 mg or carbamazepine 600–800 mg tapered to 200 mg. Withdrawal symptoms were measured using a validated CIWA-Ar tool. Patients also completed a daily drinking log to assess alcohol use prior to, during, and 7 days after study completion. The study evaluated 89 patients after the treatment period for number of drinks taken per day.
OUTCOMES MEASURED: Alcohol withdrawal symptoms and posttreatment alcohol use measured by the CIWA-Ar scale were the primary outcomes. Side effects were reported as a secondary outcome.
RESULTS: Both drugs were equally effective in reducing alcohol withdrawal symptoms. Over time, alcohol withdrawal symptoms were more likely to occur with lorazepam treatment (P = .007). After treatment, relapsing patients receiving carbamazepine had fewer drinks per day than those receiving lorazepam (1 vs 3; P = .003). Effectiveness varied based on whether patients had attempted alcohol detoxification in the past. Of the patients who reported prior multiple detoxifications, those receiving carbamazepine drank less than 1 drink per day as compared with 5 drinks per day in the lorazepam-treated group (P = .004). The overall frequency of side effects were the same for both groups; however, clinicians recorded dizziness and incoordination in more patients on lorazepam than carbamazepine (22.7% vs 6.9%; P = .02). Pruritus occurred more often in the carbamazepine group than the lorazepam group (18.9% vs 1.3%; P = .004).

ABSTRACT

BACKGROUND: Outpatient management of symptoms from acute alcohol withdrawal usually includes a tapering regimen of a benzodiazepine such as lorazepam (Ativan). Benzodiazepine use is usually limited, however, by the potential for medication abuse and side effects such as central nervous system impairment. Because studies have demonstrated that carbamazepine can be effective for the treatment of alcohol withdrawal symptoms, this study compared the effectiveness of carbamazepine with that of lorazepam.
POPULATION STUDIED: The 136 patients were self-referred and fulfilled Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for alcohol dependence and alcohol withdrawal. Patients lived within 50 miles of the study site, and had an admission blood alcohol level < 0.1 g/dL, a Mini Mental State Examination score of 26, and an admission score on the Clinical Institute Withdrawal Assessment-Alcohol, revised (CIWA-Ar) 10 out of a possible score of 20. Patients were excluded if they had substance abuse syndromes other than alcohol dependence, nicotine dependence, or cannabis abuse; major Axis I psychiatric disorder; used benzodiazepines, beta-blockers, calcium channel blockers, or antipsychotic agents within the past 30 days; a history of head injury; neurologic illness; or grossly abnormal laboratory values.
STUDY DESIGN AND VALIDITY: This was a randomized double-blind trial comparing 2 different treatments for alcohol withdrawal. Allocation to treatment group was concealed from enrolling physicians. The patients received a 5-day taper of either lorazepam 6–8 mg tapered to 2 mg or carbamazepine 600–800 mg tapered to 200 mg. Withdrawal symptoms were measured using a validated CIWA-Ar tool. Patients also completed a daily drinking log to assess alcohol use prior to, during, and 7 days after study completion. The study evaluated 89 patients after the treatment period for number of drinks taken per day.
OUTCOMES MEASURED: Alcohol withdrawal symptoms and posttreatment alcohol use measured by the CIWA-Ar scale were the primary outcomes. Side effects were reported as a secondary outcome.
RESULTS: Both drugs were equally effective in reducing alcohol withdrawal symptoms. Over time, alcohol withdrawal symptoms were more likely to occur with lorazepam treatment (P = .007). After treatment, relapsing patients receiving carbamazepine had fewer drinks per day than those receiving lorazepam (1 vs 3; P = .003). Effectiveness varied based on whether patients had attempted alcohol detoxification in the past. Of the patients who reported prior multiple detoxifications, those receiving carbamazepine drank less than 1 drink per day as compared with 5 drinks per day in the lorazepam-treated group (P = .004). The overall frequency of side effects were the same for both groups; however, clinicians recorded dizziness and incoordination in more patients on lorazepam than carbamazepine (22.7% vs 6.9%; P = .02). Pruritus occurred more often in the carbamazepine group than the lorazepam group (18.9% vs 1.3%; P = .004).

ABSTRACT

BACKGROUND: Outpatient management of symptoms from acute alcohol withdrawal usually includes a tapering regimen of a benzodiazepine such as lorazepam (Ativan). Benzodiazepine use is usually limited, however, by the potential for medication abuse and side effects such as central nervous system impairment. Because studies have demonstrated that carbamazepine can be effective for the treatment of alcohol withdrawal symptoms, this study compared the effectiveness of carbamazepine with that of lorazepam.
POPULATION STUDIED: The 136 patients were self-referred and fulfilled Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for alcohol dependence and alcohol withdrawal. Patients lived within 50 miles of the study site, and had an admission blood alcohol level < 0.1 g/dL, a Mini Mental State Examination score of 26, and an admission score on the Clinical Institute Withdrawal Assessment-Alcohol, revised (CIWA-Ar) 10 out of a possible score of 20. Patients were excluded if they had substance abuse syndromes other than alcohol dependence, nicotine dependence, or cannabis abuse; major Axis I psychiatric disorder; used benzodiazepines, beta-blockers, calcium channel blockers, or antipsychotic agents within the past 30 days; a history of head injury; neurologic illness; or grossly abnormal laboratory values.
STUDY DESIGN AND VALIDITY: This was a randomized double-blind trial comparing 2 different treatments for alcohol withdrawal. Allocation to treatment group was concealed from enrolling physicians. The patients received a 5-day taper of either lorazepam 6–8 mg tapered to 2 mg or carbamazepine 600–800 mg tapered to 200 mg. Withdrawal symptoms were measured using a validated CIWA-Ar tool. Patients also completed a daily drinking log to assess alcohol use prior to, during, and 7 days after study completion. The study evaluated 89 patients after the treatment period for number of drinks taken per day.
OUTCOMES MEASURED: Alcohol withdrawal symptoms and posttreatment alcohol use measured by the CIWA-Ar scale were the primary outcomes. Side effects were reported as a secondary outcome.
RESULTS: Both drugs were equally effective in reducing alcohol withdrawal symptoms. Over time, alcohol withdrawal symptoms were more likely to occur with lorazepam treatment (P = .007). After treatment, relapsing patients receiving carbamazepine had fewer drinks per day than those receiving lorazepam (1 vs 3; P = .003). Effectiveness varied based on whether patients had attempted alcohol detoxification in the past. Of the patients who reported prior multiple detoxifications, those receiving carbamazepine drank less than 1 drink per day as compared with 5 drinks per day in the lorazepam-treated group (P = .004). The overall frequency of side effects were the same for both groups; however, clinicians recorded dizziness and incoordination in more patients on lorazepam than carbamazepine (22.7% vs 6.9%; P = .02). Pruritus occurred more often in the carbamazepine group than the lorazepam group (18.9% vs 1.3%; P = .004).

BACKGROUND: The American Thoracic Society recommends a second- or third-generation cephalosporin with or without a macrolide for empiric treatment of community-acquired pneumonia (CAP) in hospitalized patients. These guidelines have resulted in better outcomes in patients younger than 60 years but not in older patients.¹ Azithromycin has demonstrated in vitro and in vivo activity against the common pathogens in CAP, including Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila, and Mycoplasma pneumoniae. This once-a-day macrolide possesses good tissue penetration and sustained tissue levels that allow for a shorter course of therapy.

POPULATION STUDIED: This multicenter study reported the results of 145 evaluable hospitalized patients with a primary diagnosis of CAP. The average age of these patients was not stated. Their condition was diagnosed by chest x-ray, with either one or more signs and symptoms consistent with lower respiratory infection or an elevated white blood cell count. Patients were excluded if they were allergic to the study drugs, had been hospitalized during the previous 14 days, were immunosuppressed, had serious renal dysfunction or conditions affecting drug absorption, or took an antibiotic within 24 hours of enrollment.

STUDY DESIGN AND VALIDITY: This was a prospective randomized unblinded trial comparing the empiric treatment of CAP with 2 regimens. One group of patients received intravenous azithromycin 500 mg daily for 2 to 5 days followed by oral therapy to complete a 7- to 10-day course. The second group was treated with the combination of intravenous cefuroxime 750 mg every 8 hours for 2 to 7 days followed by oral cefuroxime 500 mg twice a day for a complete 7- to 10-day course along with erythromycin lactobionate or base 500 mg to 1 g intravenously every 6 hours and then orally for a total of 21 days. This study was well done, with several limitations. Concealed allocation of randomization occurred through the use of opaque envelopes after each patient was stratified by risk factors. The sample size was large enough to find a 14% difference in clinical response rates with a power of 80%. Analysis was by intention to treat. Few data (such as all-important age) were provided about the type of patients in this study, making it difficult to make generalizations. Also, the evaluators of clinical response were aware of what treatment the patient received. Given the subjective nature of the end points of “cure” versus “failure,” this lack of blinding could have affected these outcome measures. However, end points such as “time to cure” (not evaluated in this study) would be more likely to be affected by observer bias.

OUTCOMES MEASURED: Clinical response (success/failure) was the primary outcome. Adverse events and in-hospital mortality were secondary end points.

RESULTS: The causative infecting organism was not known in 41% of the patients. The most common causative agents in patients with definitive or presumptive diagnoses were: S pneumonaie (19%), L pneumophila (14%), and H influenzae (13%). The rate of cure of patients with CAP was similar: azithromycin 75% (95% confidence interval [CI], 64%-84%) and cefuroxime plus erythromycin 83% (95% CI, 73%-90%). Cure rates did not differ by causative organism. Adverse effects occurred significantly more often in the cefuroxime/erythromycin-treated patients (P <.001), due in large part to catheter site reactions and gastrointestinal tract symptoms presumably related to erythromycin. Mortality was similar in the 2 groups

BACKGROUND: The American Thoracic Society recommends a second- or third-generation cephalosporin with or without a macrolide for empiric treatment of community-acquired pneumonia (CAP) in hospitalized patients. These guidelines have resulted in better outcomes in patients younger than 60 years but not in older patients.¹ Azithromycin has demonstrated in vitro and in vivo activity against the common pathogens in CAP, including Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila, and Mycoplasma pneumoniae. This once-a-day macrolide possesses good tissue penetration and sustained tissue levels that allow for a shorter course of therapy.

POPULATION STUDIED: This multicenter study reported the results of 145 evaluable hospitalized patients with a primary diagnosis of CAP. The average age of these patients was not stated. Their condition was diagnosed by chest x-ray, with either one or more signs and symptoms consistent with lower respiratory infection or an elevated white blood cell count. Patients were excluded if they were allergic to the study drugs, had been hospitalized during the previous 14 days, were immunosuppressed, had serious renal dysfunction or conditions affecting drug absorption, or took an antibiotic within 24 hours of enrollment.

STUDY DESIGN AND VALIDITY: This was a prospective randomized unblinded trial comparing the empiric treatment of CAP with 2 regimens. One group of patients received intravenous azithromycin 500 mg daily for 2 to 5 days followed by oral therapy to complete a 7- to 10-day course. The second group was treated with the combination of intravenous cefuroxime 750 mg every 8 hours for 2 to 7 days followed by oral cefuroxime 500 mg twice a day for a complete 7- to 10-day course along with erythromycin lactobionate or base 500 mg to 1 g intravenously every 6 hours and then orally for a total of 21 days. This study was well done, with several limitations. Concealed allocation of randomization occurred through the use of opaque envelopes after each patient was stratified by risk factors. The sample size was large enough to find a 14% difference in clinical response rates with a power of 80%. Analysis was by intention to treat. Few data (such as all-important age) were provided about the type of patients in this study, making it difficult to make generalizations. Also, the evaluators of clinical response were aware of what treatment the patient received. Given the subjective nature of the end points of “cure” versus “failure,” this lack of blinding could have affected these outcome measures. However, end points such as “time to cure” (not evaluated in this study) would be more likely to be affected by observer bias.

OUTCOMES MEASURED: Clinical response (success/failure) was the primary outcome. Adverse events and in-hospital mortality were secondary end points.

RESULTS: The causative infecting organism was not known in 41% of the patients. The most common causative agents in patients with definitive or presumptive diagnoses were: S pneumonaie (19%), L pneumophila (14%), and H influenzae (13%). The rate of cure of patients with CAP was similar: azithromycin 75% (95% confidence interval [CI], 64%-84%) and cefuroxime plus erythromycin 83% (95% CI, 73%-90%). Cure rates did not differ by causative organism. Adverse effects occurred significantly more often in the cefuroxime/erythromycin-treated patients (P <.001), due in large part to catheter site reactions and gastrointestinal tract symptoms presumably related to erythromycin. Mortality was similar in the 2 groups

BACKGROUND: The American Thoracic Society recommends a second- or third-generation cephalosporin with or without a macrolide for empiric treatment of community-acquired pneumonia (CAP) in hospitalized patients. These guidelines have resulted in better outcomes in patients younger than 60 years but not in older patients.¹ Azithromycin has demonstrated in vitro and in vivo activity against the common pathogens in CAP, including Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila, and Mycoplasma pneumoniae. This once-a-day macrolide possesses good tissue penetration and sustained tissue levels that allow for a shorter course of therapy.

POPULATION STUDIED: This multicenter study reported the results of 145 evaluable hospitalized patients with a primary diagnosis of CAP. The average age of these patients was not stated. Their condition was diagnosed by chest x-ray, with either one or more signs and symptoms consistent with lower respiratory infection or an elevated white blood cell count. Patients were excluded if they were allergic to the study drugs, had been hospitalized during the previous 14 days, were immunosuppressed, had serious renal dysfunction or conditions affecting drug absorption, or took an antibiotic within 24 hours of enrollment.

STUDY DESIGN AND VALIDITY: This was a prospective randomized unblinded trial comparing the empiric treatment of CAP with 2 regimens. One group of patients received intravenous azithromycin 500 mg daily for 2 to 5 days followed by oral therapy to complete a 7- to 10-day course. The second group was treated with the combination of intravenous cefuroxime 750 mg every 8 hours for 2 to 7 days followed by oral cefuroxime 500 mg twice a day for a complete 7- to 10-day course along with erythromycin lactobionate or base 500 mg to 1 g intravenously every 6 hours and then orally for a total of 21 days. This study was well done, with several limitations. Concealed allocation of randomization occurred through the use of opaque envelopes after each patient was stratified by risk factors. The sample size was large enough to find a 14% difference in clinical response rates with a power of 80%. Analysis was by intention to treat. Few data (such as all-important age) were provided about the type of patients in this study, making it difficult to make generalizations. Also, the evaluators of clinical response were aware of what treatment the patient received. Given the subjective nature of the end points of “cure” versus “failure,” this lack of blinding could have affected these outcome measures. However, end points such as “time to cure” (not evaluated in this study) would be more likely to be affected by observer bias.

OUTCOMES MEASURED: Clinical response (success/failure) was the primary outcome. Adverse events and in-hospital mortality were secondary end points.

RESULTS: The causative infecting organism was not known in 41% of the patients. The most common causative agents in patients with definitive or presumptive diagnoses were: S pneumonaie (19%), L pneumophila (14%), and H influenzae (13%). The rate of cure of patients with CAP was similar: azithromycin 75% (95% confidence interval [CI], 64%-84%) and cefuroxime plus erythromycin 83% (95% CI, 73%-90%). Cure rates did not differ by causative organism. Adverse effects occurred significantly more often in the cefuroxime/erythromycin-treated patients (P <.001), due in large part to catheter site reactions and gastrointestinal tract symptoms presumably related to erythromycin. Mortality was similar in the 2 groups